Mafosfamide, a cyclophosphamide analog, causes a proinflammatory response and increased permeability on endothelial cells in vitro.
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
28
09
2022
accepted:
05
01
2023
revised:
21
12
2022
medline:
6
4
2023
pubmed:
14
1
2023
entrez:
13
1
2023
Statut:
ppublish
Résumé
Post-transplantation cyclophosphamide (PTCy) has decreased GVHD incidence. Endothelial damage in allo-HCT is caused by multiple factors, including conditioning treatments and some immunosupressants, and underlies HCT-complications as GVHD. Nevertheless, the specific impact of PTCy on the endothelium remains unclear. We evaluated the effect of mafosfamide (MAF), an active Cy analog, on endothelial cells (ECs) vs. cyclosporine A (CSA), with known damaging endothelial effect. ECs were exposed to MAF and CSA to explore changes in endothelial damage markers: (i) surface VCAM-1, (ii) leukocyte adhesion on ECs, (iii) VE-cadherin expression, (iv) production of VWF, and (v) activation of intracellular signaling proteins (p38MAPK, Akt). Results obtained (expressed in folds vs. controls) indicate that both compounds increased VCAM-1 expression (3.1 ± 0.3 and 2.8 ± 0.6, respectively, p < 0.01), with higher leukocyte adhesion (5.5 ± 0.6, p < 0.05, and 2.8 ± 0.4, respectively). VE-cadherin decreased with MAF (0.8 ± 0.1, p < 0.01), whereas no effect was observed with CSA. Production of VWF augmented with CSA (1.4 ± 0.1, p < 0.01), but diminished with MAF (0.9 ± 0.1, p < 0.05). p38MAPK activation occurred with both compounds, being more intense and faster with CSA. Both drugs activated Akt, with superior MAF effect at longer exposure. Therefore, the cyclophosphamide analog MAF is not exempt from a proinflammatory effect on the endothelium, though without modifying the subendothelial characteristics.
Identifiants
pubmed: 36639572
doi: 10.1038/s41409-023-01912-w
pii: 10.1038/s41409-023-01912-w
doi:
Substances chimiques
mafosfamide
5970HH9923
Vascular Cell Adhesion Molecule-1
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
von Willebrand Factor
0
Cyclophosphamide
8N3DW7272P
Cyclosporine
83HN0GTJ6D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
407-413Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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